GH deficiency (GHD) in adults has been associated with changes in body composition, cardiovascular function, metabolic parameters associated with cardiovascular risk, and bone density and metabolism. These observations have been used to advocate GH therapy in GHD adults. However, the studies published to date were mostly done in patients who are often chronically sick, lack other pituitary hormones whose replacement therapies may not be optimal, and/or have had radiation therapy (all factors able to influence morbidity). Reliable data on the consequences of GHD can only be obtained by studying patients that are otherwise healthy. A large population of GH-naive adults with GHD due to a homozygous mutation of the GHRH receptor (GHRHR) gene resides in Brazil (Itabaianinha county). We propose to study the subjects homozygous for this mutation and compare them with normal subjects from the same community. Our primary goal is to determine the consequences of life-long GHD on body composition, cardiovascular function and risk factors, bone density and metabolism, and thyroid status, and to test which of these parameters are reversed by 6 months of hGH replacement therapy. The secondary goal is to test the hypothesis that heterozygosity for the mutation causes a phenotype that is intermediate between homozygous normal and GHD individuals. [unreadable] SPECIFIC AIM 1: to study body composition, cardiovascular status, cardiovascular risk profile, metabolic parameters, thyroid status, and bone mineral density in twenty GH-naive GHD subjects and compare them with twenty age- and sex-matched controls from the same community. [unreadable] SPECIFIC AIM 2: to examine the response of GHD individuals to 6 months therapy with GH. [unreadable] SPECIFIC AIM 3: to genotype a large number of apparently normal members of the ltabaianinha community to separate subjects homozygous for the wild-type allele from subjects heterozygous for the GHRHR mutation, and to compare the phenotype of one hundred heterozygotes with the one observed in one hundred homozygous normal individuals. [unreadable] [unreadable]